Menard T W, Osgood T B, Clark J I, Spence A M, Steele J E, Krohn K A, Livesey J C
Int J Radiat Oncol Biol Phys. 1986 Aug;12(8):1483-6. doi: 10.1016/0360-3016(86)90199-9.
Protection by WR-77913 against radiation-induced cataract formation in rats was observed following intraperitoneal (i.p.) administration of drug (1160 mg/kg) 15-30 min before exposure to 15.3 Gy of Cs-137 whole head irradiation. Control groups included irradiated, non-protected animals, and sham-irradiated aging controls. Protection was documented photographically and by analysis of eye lens constituents. All non-protected irradiated animals developed dense cataracts throughout the lens between 90-120 days post-irradiation, while WR-77913 protected animals developed minimal lens opacification through 200 days post-irradiation. No opacification in aging controls was seen. Lens protein analysis by Lowry assay and size exclusion HPLC showed radioprotected and aging control animals were similar in protein content, distribution of total and soluble protein, and degree of lens hydration. This contrasted significantly with cataractous lenses of non-protected animals. In cataractous lenses, the soluble protein concentration in the 25-43 K dalton range was approximately 10% of that found in radioprotected or aging control lenses. Hydration was substantially higher in cataractous lens. These results indicate that WR-77913 protects against lens opacification, protein insolubilization, and hydration in lenses of irradiated animals. Biodistribution studies with [S-35]-WR-77913 showed ocular uptake of drug within 15 minutes after i.p. injection, which remained relatively constant through 60 min. The relative order of drug concentration for individual eye components was: globe greater than total eye approximately equal to humor greater than lens. Although the mechanism of radioprotection observed remains to be elucidated, WR-77913 clearly prevents radiation-induced cataracts in rats. The potentially significant clinical use for this radioprotective compound is being investigated further.
在大鼠接受15.3 Gy的铯-137全脑照射前15 - 30分钟腹腔注射药物（1160毫克/千克）WR - 77913后，观察到其对辐射诱导的白内障形成具有保护作用。对照组包括接受照射但未受保护的动物以及假照射的老龄对照动物。通过摄影及对晶状体成分的分析记录保护效果。所有未受保护的照射动物在照射后90 - 120天内晶状体全层出现致密白内障，而接受WR - 77913保护的动物在照射后200天内晶状体浑浊程度最小。老龄对照动物未见浑浊。通过Lowry法和尺寸排阻高效液相色谱法进行的晶状体蛋白分析表明，受辐射保护的动物和老龄对照动物在蛋白含量、总蛋白和可溶性蛋白分布以及晶状体水合程度方面相似。这与未受保护动物的白内障晶状体形成显著对比。在白内障晶状体中，25 - 43千道尔顿范围内的可溶性蛋白浓度约为受辐射保护或老龄对照晶状体中的10%。白内障晶状体中的水合程度显著更高。这些结果表明，WR - 77913可保护受照射动物的晶状体不发生浑浊、蛋白不溶性化和水合。用[S - ³⁵] - WR - 77913进行的生物分布研究表明，腹腔注射后15分钟内药物被眼部摄取，至60分钟时保持相对恒定。各眼部成分药物浓度的相对顺序为：眼球大于全眼约等于房水大于晶状体。尽管所观察到的辐射防护机制仍有待阐明，但WR - 77913显然可预防大鼠辐射诱导的白内障。正在进一步研究这种辐射防护化合物潜在的重要临床用途。
